Effects of grape seed proanthocyanidin extract on lipopolysaccharide translocation and trafficking from the gut to tissues

Diet-associated alterations of the intestinal barrier and gut microbiota promote intestinal lipopolysaccharide (LPS) translocation from the lumen to the lamina propria through different pathways, leading to an increase in LPS levels in the plasma known as metabolic endotoxemia.As a pharmacological dose of grape seed proanthocyanidin extract (GSPE) can reduce metabolic endotoxemia of obese rats, in the current study, we aimed to evaluate GSPE modulation of LPS translocation and the un-derlying mechanisms. We performed both an in vitro experiment with Caco-2 cells and an in vivo experiment with Wistar female rats fed a cafeteria (CAF) diet. GSPE was effective in regulating intestinal permeability through the modulation of receptor-mediated endocytosis pathway, as well as the gut microbiota interaction with the endocannabinoid system through epigenetic mechanisms. Our results confirm that GSPE can ameliorate intes-tinal dysfunction and metabolic endotoxemia caused by an excess of dietary lipids by modulating the endotoxin-translocation pathways.